GAGE12H

Chr X

G antigen 12H

NCBI Gene: 729442ENSG00000224902UniProt: A6NDE8OMIM: 300732

The GAGE12H protein is a member of the G antigen family, but its specific cellular function remains poorly characterized. Mutations in this gene have been associated with neurodevelopmental disorders, though the clinical phenotype and inheritance pattern are not well-established in the current literature. This gene shows relatively low constraint against loss-of-function variants based on population genetic data.

OMIMResearch
MultiplemechanismLOEUF 1.82
Clinical Summary— GAGE12H
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
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ClinVar Variants
58 unique Pathogenic / Likely Pathogenic· 58 VUS of 120 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.82LOEUF
pLI 0.345
Z-score 0.71
OE 0.00 (0.00–1.82)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.05Z-score
OE missense 3.37 (1.54–1.99)
20 obs / 5.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.00 (0.00–1.82)
0≤0.351.4
Missense OE3.37 (1.54–1.99)
0≤0.61.4
Synonymous OE0.96
0≤1.21.6
LoF obs/exp: 0 / 0.6Missense obs/exp: 20 / 5.9Syn Z: 0.05
DN
0.6259th %ile
GOF
0.6542th %ile
LOF
0.1399th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

120 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic2
VUS58
Likely Benign4
56
Pathogenic
2
Likely Pathogenic
58
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
56
0
56
Likely Pathogenic
0
0
2
0
2
VUS
1
48
9
0
58
Likely Benign
0
4
0
0
4
Benign
0
0
0
0
0
Total152670120

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GAGE12H · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients